Predicting Response to Standard First-line Treatment in High-grade Serous Ovarian Carcinoma by Angiogenesis-related Genes
ANTICANCER RESEARCH
Authors: Mendiola, Marta; Redondo, Andres; Heredia-Soto, Victoria; Herranz, Jesus; Berjon, Alberto; Hernandez, Alicia; Miguel-Martin, Maria; Crespo, Roberto; Barriuso, Jorge; Cruz, Patricia; Yebenes, Laura; Pelaez-Garcia, Alberto; Castelo, Beatriz; Ramirez De Molina, Ana; Feliu, Jaime; Hardisson, David
Abstract
Background/Aim: Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for firstline chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. Materials and Methods: Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan lowdensity arrays. Results: Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan-Meier survival curves were used to estimate the accuracy of these predictors. Conclusion: An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC.
Bioinformatics analysis to identify key genes and pathways influencing synovial inflammation in osteoarthritis
MOLECULAR MEDICINE REPORTS
Authors: Lin, Jie; Wu, Guangwen; Zhao, Zhongsheng; Huang, Yanfeng; Chen, Jun; Fu, Changlong; Ye, Jinxia; Liu, Xianxiang
Abstract
Osteoarthritis (OA) is a chronic arthropathy that occurs in the middle-aged and elderly population. The present study aimed to identify gene signature differences between synovial cells from OA synovial membrane with and without inflammation, and to explain the potential mechanisms involved. The differentially expressed genes (DEGs) between 12 synovial membrane with inflammation and 12 synovial membrane without inflammation from the dataset GSE46750 were identified using the Gene Expression Omnibus 2R. The DEGs were subjected to enrichment analysis, protein-protein interaction (PPI) analysis and module analysis. The analysis results were compared with text-mining results. A total of 174 DEGs were identified. Gene Ontology enrichment results demonstrated that functional molecules encoded by the DEGs primarily had extracellular location, molecular functions predominantly involving chemokine activity' and cytokine activity', and were associated with biological processes, including inflammatory response' and immune response'. The Kyoto Encyclopedia of Genes and Genomes results demonstrated that DEGS may function through pathways associated with rheumatoid arthritis', chemokine signaling pathway', complement and coagulation cascades', TNF signaling pathway', intestinal immune networks for IgA production', cytokine-cytokine receptor interaction', allograft rejection', Toll-like receptor signaling pathway' and antigen processing and presentation'. The top 10 hub genes [interleukin (IL)6, IL8, matrix metallopeptidase (MMP)9, colony stimulating factor 1 receptor, FOS proto-oncogene, AP1 transcription factor subunit, insulin-like growth factor 1, TYRO protein tyrosine kinase binding protein, MMP3, cluster of differentiation (CD)14 and CD163] and four gene modules were identified from the PPI network using Cytoscape. In addition, text-mining was used to identify the commonly used drugs and their targets for the treatment of OA. It was initially verified whether the results of the present study were useful for the study of OA treatment targets and pathways. The present study provided insight for the molecular mechanisms of OA synovitis. The hub genes and associated pathways derived from analysis may be targets for OA treatment. IL8 and MMP9, which were validated by text-mining, may be used as molecular targets for the OA treatment, while other hub genes require further validation.